View source for 6qex


==Nanodisc reconstituted human ABCB1 in complex with UIC2 fab and taxol==
<SX load='6qex' size='340' side='right' viewer='molstar' caption='[[6qex]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qex]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QEX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TA1:TAXOL'>TA1</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6qee|6qee]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABCB1, MDR1, PGY1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/ABC-type_xenobiotic_transporter ABC-type xenobiotic transporter], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=7.6.2.2 7.6.2.2] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6qex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qex OCA], [https://pdbe.org/6qex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qex RCSB], [https://www.ebi.ac.uk/pdbsum/6qex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qex ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/MDR1_HUMAN MDR1_HUMAN]] Ulcerative colitis. Disease susceptibility is associated with variations affecting the gene represented in this entry. 
== Function ==
[[https://www.uniprot.org/uniprot/MDR1_HUMAN MDR1_HUMAN]] Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ABCB1, also known as P-glycoprotein, actively extrudes xenobiotic compounds across the plasma membrane of diverse cells, which contributes to cellular drug resistance and interferes with therapeutic drug delivery. We determined the 3.5-angstrom cryo-electron microscopy structure of substrate-bound human ABCB1 reconstituted in lipidic nanodiscs, revealing a single molecule of the chemotherapeutic compound paclitaxel (Taxol) bound in a central, occluded pocket. A second structure of inhibited, human-mouse chimeric ABCB1 revealed two molecules of zosuquidar occupying the same drug-binding pocket. Minor structural differences between substrate- and inhibitor-bound ABCB1 sites are amplified toward the nucleotide-binding domains (NBDs), revealing how the plasticity of the drug-binding site controls the dynamics of the adenosine triphosphate-hydrolyzing NBDs. Ordered cholesterol and phospholipid molecules suggest how the membrane modulates the conformational changes associated with drug binding and transport.

Structural insight into substrate and inhibitor discrimination by human P-glycoprotein.,Alam A, Kowal J, Broude E, Roninson I, Locher KP Science. 2019 Feb 15;363(6428):753-756. doi: 10.1126/science.aav7102. PMID:30765569<ref>PMID:30765569</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qex" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</SX>
[[Category: ABC-type xenobiotic transporter]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Alam, A]]
[[Category: Locher, K P]]
[[Category: Abc transporter]]
[[Category: Abcb1]]
[[Category: Membrane protein]]
[[Category: Multidrug exporter]]
[[Category: P-glycoprotein]]
[[Category: P-gp]]